Without limiting the scope of the invention, its background is described in connection with piggy-back delivery of nucleic acids into organisms.
U.S. Pat. No. 7,935,816 issued to Yong-Fu Li (2011) describes preparations of molecular transporter compositions and their use for transporting bioactive substances into cells in living animals. For in vivo delivery, the composition is covalently linked to the bioactive substance and the resultant composite structure is introduced into the subject. The transporter composition includes multiple guanidine moieties on a dendrimeric scaffold having a triazine core.
U.S. Patent Application Publication No. 20110190287 to Pudur Jagadeeswaran (2011) describes compounds comprising a guanidine-rich head covalently coupled to one or more oligonucleotide antisense sequences which are useful to modulate blood coagulation by affecting the expression of integrin α.IIb or β.3. Included are also pharmaceutical compositions containing these compounds, with or without other therapeutic agents, and well as methods of using these compounds as inhibitor of platelet aggregation, as thrombolytics, and/or for the treatment of other thromboembolic disorders. Vivo-MOs, which include eight guanidine groups dendrimerically arranged in the guanidine-rich head and two synthetic antisense morpholino oligonucleotides, are representative compounds.
U.S. Patent Application Publication No. 20100292306 to George Carlson et al (2010) describes compositions and methods for treatment of individuals diagnosed with a dystrophin deficiency are disclosed. In particular, inhibitors of NF.K.B transactivation and/or inhibitors that suppress p65 expression are used to prevent and/or reverse muscle damage in animals or humans lacking dystrophin. Such compositions and methods are useful in the treatment of individuals with muscular dystrophy. In an embodiment of the present disclosure a subject diagnosed with Duchenne mucular dystrophy may be treated with an agent that is a specific translation blocking vivo-morpholino to decrease the level or the activity of the p65 subunit of NF.K.B in the muscular tissues of the subject.
Wu et al., Targeted skipping of human dystrophin exons in transgenic mouse model systemically for antisense drug development, PLoS One. 2011; 6(5):e19906. Epub 2011 May 17, describes application of vivo-morpholino to a hDMD mouse, a transgenic model carrying the full-length human dystrophin gene, and more than 70% efficiency of targeted human dystrophin exon skipping in vivo systemically. We also established a GFP-reporter myoblast culture to screen AOs targeting human dystrophin exon 50. Antisense efficiency for most AOs was consistent between the reporter cells, human myoblasts and in the hDMD mice in vivo. But variation in efficiency was also clearly observed.
Nazmi et al, Antiviral and neuroprotective role of octaguanidinium dendrimer-conjugated morpholino oligomers in Japanese encephalitis, PLoS Negl Trop Dis. 2010 Nov. 23; 4(11):e892.